Identifying and characterizing chemical skin sensitizers without animal testing: Colipa’s research and method development program

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

“…In the area of data collection and in silico approaches, metabolite identification and protein binding in cellbased assays should be addressed. Furthermore, re-record of past and present activity in this area (Adler et al, 2011;Aeby et al, 2010;Basketter and Maxwell, 2007;Basketter, 2008;Basketter and Kimber, 2011;Bauch et al, 2011;De Silva et al, 1995;dos Santos et al, 2009;Hartung et al, 2011;Kimber et al, 1999bKimber et al, , 2001Kimber et al, , 2010Kimber et al, , 2011Martin et al, 2010;Maxwell and Mackay, 2008;Patlewicz et al, 2007;Reuter et al, 2011;Ryan et al, 2005;Vandebriel and van Loveren, 2010). However, our intention here is not to provide yet another scholarly review article.…”

“…There is a need for a critical evaluation of the strengths and limitations of novel methods compared with existing in vivo models, even with their limitations. -For the evaluation and validation of new methods (of whatever type) there is a need to evaluate specificity, sensitivity, 2010), as well as a variety of cellular assays based on the use of cultured DC or DC-like cells (Aeby et al, 2010;Ashikaga et al, 2010;Reuter et al, 2011;Sakaguchi et al, 2006;Johansson et al, 2011). It would be interesting to evaluate, prospectively and with an unbiased set of chemicals, how such an expert panel (with access to QSAR models and data derived from selected in vitro tests) would fare compared with the LLNA or with human ACD.…”

Integrating non-animal test information into an adaptive testing strategy – skin sensitization proof of concept case

“…Many research groups are working on the development of alternative tests for skin sensitization (Vandebriel and van loveren, 2010;Aeby et al, 2010). As a chemical's reactivity towards proteins is deemed a key determining factor in its ability to act as a skin sensitizer, a lot of research has focused on in chemico measurements of reactivity with model nucleophiles.…”

“…to further elucidate the skin sensitization induction process, various measures of dendritic cell activation are considered. Recent advances in the in vitro generation of immature dendritic cells and the availability of cell line surrogates with various DC-like characteristics has led to the development of in vitro tests based on the measurement of various cell surface markers or secretion of cytokines modulated upon exposure to chemicals (Aeby et al, 2010;Ryan et al, 2005;lambrechts et al, 2010). Numerous attempts were also made to predict in silico the skin sensitization potential in vivo (Roberts et al, 2007;Patlewicz et al, 2007Patlewicz and Worth, 2008;Karlberg et al, 2008).…”

The Adverse Outcome Pathway for Skin Sensitisation Initiated by Covalent Binding to Proteins

“…Due to the biological complexity (e.g. multiple organs and multiple cell types), skin sensitisation has historically been and continues to be evaluated with in vivo tests although alternative methods are under development and prevalidation (see Aeby et al, 2010;Adler et al, 2011).…”